As a component of the Adult AIDS Clinical Trials Group, the UCSF AACTG unit's (AACTU) primary aims will be to advance the AACTG's research objectives in the areas of pathogenesis and therapeutics of opportunistic infections and metabolic and neurologic complications of HIV disease and in pharmacologic issues related to the drugs used to treat HIV disease. In the project period, this unit's focus will emphasize scientific leadership and subject accrual in studies designed to investigate the natural history and pathogenesis of HIV-related complications in the HAART era, to improve strategies and therapies for preventing and treating these complications, and to use pharmacologic and behavioral science expertise to increase the scientific understanding and clinically relevant knowledge about treatment for HIV disease. The unit plans to enroll 100 new subjects into a variety of trials and substudies each year and to follow these and at least 100 continuing subjects, maintaining compliance with the AACTG's high standards for protocol adherence, data management, and subject retention. Dr. Mark Jacobson, the Principal Investigator of this unit, will continue to be one of the group's key scientific leaders in investigating the treatment, prophylaxis and immunopathogenesis of AIDS-related opportunistic infections. Dr. Kathy Mulligan will continue to be one of the key leaders in the effort to understand, prevent and treat the metabolic complications of HAART. Drs. Francesca Aweeka, Lewis Sheiner, and John Gambertoglio will be leaders of the group's efforts to understand pharmacokinetic (PK) interactions among drugs used to manage HIV infection and its complications; to use statistical simulation for optimizing study designs for explanatory PK/pharmacodynamic and pathophysiologic analyses and adaptive therapy strategies; and to maintain high interlaboratory quality control and assurance for specific drug assays. Dr. Margaret Chesney will lead the group effort to develop standardized measures of adherence that can be easily applied across protocols to evaluate relationships between adherence and clinical, virologic and immunologic outcomes, as well as to test interventions to increase medication adherence. Dr. Paul Volberding will lead the group's first effort to determine how best to utilize intensive combination antiretroviral regimens in acute/early HIV infection in order to maintain long-term suppression of HIV infection. Dr. J. M. McCune will provide expertise and laboratory support for immunologic studies, and Drs. Richard Price and Harry Hollander will provide clinical expertise to support neurologic studies.